title: New cyclic somatostatin analogues containing a pyrazinone ring: importance of Tyr for antiproliferative activity.
abstract: Novel somatostatin analogues containing a pyrazinone ring, compounds 1 and 2, exhibited good antiproliferative activity on A431 tumor cells. To increase antitumor activity and binding affinity on somatostatin receptors (SSTRs), we substituted Tyr in the critical sequence, Tyr-D-Trp-Lys, with more hydrophobic aromatic residue. The substituted compounds dramatically lost antitumor activity, indicating that Tyr residue was an essential residue.
authors.affiliation: Faculty of Pharmaceutical Sciences, Department of Medicinal Chemistry, Kobe Gakuin University, Nishi-ku, Kobe 651-2180, Japan.
authors.forename: Anna
authors.initials: A
authors.lastname: Miyazaki
authors.forename: Yuko
authors.initials: Y
authors.lastname: Tsuda
authors.forename: Shoji
authors.initials: S
authors.lastname: Fukushima
authors.forename: Toshio
authors.initials: T
authors.lastname: Yokoi
authors.forename: Tibor
authors.initials: T
authors.lastname: Vántus
authors.forename: Gyöngyi
authors.initials: G
authors.lastname: Bökönyi
authors.forename: Edit
authors.initials: E
authors.lastname: Szabó
authors.forename: Anikó
authors.initials: A
authors.lastname: Horváth
authors.forename: György
authors.initials: G
authors.lastname: Kéri
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Okada
mesh_terms: D000595:Amino Acid Sequence; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D011719:Pyrazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017481:Receptors, Somatostatin / Q000187:drug effects*; D013004:Somatostatin / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014443:Tyrosine / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D011719:Pyrazines; D017481:Receptors, Somatostatin; D014443:Tyrosine; D013004:Somatostatin